EP3276342A1 - Method for calibrating a gas chromatograph - Google Patents

Abstract

In order to make the calibration of a gas chromatograph (1) more failsafe, the relative response factors (RRF) determined during the calibration are compared with universal relative response factors (uRRF) contained in a memory (25) and typical for the detectors (12, 13). If the relative response factors (RRF) determined during the calibration deviate from the universal relative response factors (uRRF) by more than a predetermined amount, an error message (27) is generated and output. This is based on the knowledge that the detectors (12, 13) used today have a very high reproducibility due to mass production. As a result, the relative response factors (RRF) are virtually invariable and have a universal character. The universal relative response factors (uRRF) can therefore, for. As the manufacturer of the detectors are determined and provided for different components.

Description

The invention relates to a method for calibrating a gas chromatograph and a gas chromatograph.

Such as B. from the WO 03/083467 A2 In the gas chromatographic analysis of a mixture of substances, a metered sample of the (gaseous or if necessary evaporated) mixture of substances is passed through a chromatographic separator with the aid of a carrier gas. The components of the mixture are separated due to different retention times so that they appear sequentially at the output of the separator. There, the individually emerging components are detected by means of a suitable detector. These are different types of detectors such. B. Thermal conductivity detectors or flame ionization detectors available. The thermal conductivity detector used in most cases compares the thermal conductivity of the currently detected component with that of the carrier gas, thereby generating a detector response in the form of a (ideally Gaussian) peak, the area of which is normally proportional to the amount of component detected. Over the duration of the analysis of the mixture of substances, the detector thus generates a chromatogram in which the local or temporal positions of the peaks, the different components and the peak areas (or, in a simplistic view, the peak heights) denote the quantities of the components in the sample of the mixture mixed with the gas chromatograph , By evaluating the chromatogram, the concentrations of the different components in the mixture are determined.

While a separation column is sufficient as a separation device for the separation of simple mixtures, complex mixtures require a column circuit in which two or more columns with different separation properties in series and possibly connected in parallel. In this case, the individual separation columns detectors (usually heat conductivity detectors) downstream, which detect the eluting components non-destructive and together form a detector device.

The detector response, in particular the peak area used for the quantitative determination of the detected component, is primarily dependent on the component, its quantity and the detector used in each case. In addition, the detector response is influenced by different measurement conditions such as temperature, pressure and flow rate of the carrier gas, operating voltage of the detector, amplification of the raw detector signal, etc.

It is therefore necessary to calibrate the gas chromatograph for the different components to be determined of each gas mixture to be analyzed.

The calibration can be done individually for each component to be determined by the gas chromatograph is given a calibration sample containing the respective component in a known concentration c _i . This makes it possible to determine an absolute response factor RF _i = A _{i, cal} / c _{i, cal} for the detector, where c _{i, cal denote} the concentration of component i in the calibration sample and A _{i / cal} the resulting detector response in the form of the peak area. Assuming that the same measuring conditions as in the calibration are present in the analysis of a gas mixture containing the component i in unknown concentration (in particular also the metered sample quantity being the same) and the detector behaves linearly over the concentration measuring range, the concentration c _{i of} the Component i can be determined using the determined absolute response factor RF _i from the detector response A _i with c _i = A _i / RF _i . For nonlinear behavior of the detector, calibration must be performed with multiple calibration samples with different known component concentration values to create a calibration curve for the detector.

Since it is very difficult to reproducibly dose the same amount of sample each time with high accuracy, it is known to add to each of the calibration sample and the samples of gas mixtures to be analyzed an internal standard IS in a certain concentration c _IS . After the response factors RF _i and RF _IS = A _IS / c _IS i and the standard IS were determined in the calibration for the component can be in the analysis of the concentration c _i of component i in the detector response A _i, c _i = c _IS · (A _i · RF _IS ) / (RF _i · A _IS ). The unknown concentration c _i is thus measured in relation to the known concentration c _IS , which ratio is independent of the respectively metered amount of sample.

The response factor RF _{i of} the component i can be set in relation to the response factor RF _{IS of} the standard IS, so that one obtains a relative response factor RRF _i-IS = RF _i / RF _IS , on the basis of which the concentration c _{i of} the component i c _i = c _IS · (1 / RRF _i-IS ) · (A _i / A _IS ).

Relative response factors can generally be used to determine an unknown concentration c _{i of} a first component i of a substance mixture in the presence of a second component (reference component) k whose concentration c _{k is} known. It is thus also possible to measure the concentrations c _i of components i for which no separate response factor RF _i exists or was determined by calibration: c _i = c _k * (1 / RRF _ik ) * (A _i / A _k ) = A _i / (RF _k * RRF _ik ).

The relative response factors RRF _ik must also be determined as part of a calibration. The advantage of their use lies in the fact that they are independent of the metered sample quantity (dosage amount) and the measuring conditions in a reasonable scope; new components can be added to the calibration mixture, and it is possible to convert the relative response factors to other reference components; So z. For example: RRF _jk = RRF _ji * RRF _ik . The concentration c _{j of} a component j can therefore be determined with known relative response factors if the relative response factor RRF _jk is unknown Determine RRF _ji and RRF _ik as follows: $${\mathrm{c}}_{\mathrm{j}}={\mathrm{c}}_{\mathrm{k}}\cdot \left(\mathrm{1}/\left({\mathrm{RRF}}_{\mathrm{j}-\mathrm{i}}\cdot {\mathrm{RRF}}_{\mathrm{i}-\mathrm{k}}\right)\right)\cdot \left({\mathrm{A}}_{\mathrm{j}}/{\mathrm{A}}_{\mathrm{k}}\right)={\mathrm{A}}_{\mathrm{j}}/\left({\mathrm{RF}}_{\mathrm{k}}\cdot {\mathrm{RRF}}_{\mathrm{j}-\mathrm{i}}\cdot {\mathrm{RRF}}_{\mathrm{i}-\mathrm{k}}\right)\mathrm{,}$$

• " Guidelines for the quantitative gas chromatography of volatile flavouring substances, from the Working Group on Methods of Analysis of the International Organization of the Flavor Industry (IOFI)", Flavour and Fragrance Journal, 2011, 26, 297-299 .

Response factors can also be defined and calculated elsewhere, for example as reciprocal of the factors explained above. The prior art refers to the following references:

• " Guidelines for the Quantitative Gas Chromatography of Volatile Flavoring Substances, from the Working Group on Methods of Analysis of the International Organization of the Flavor Industry (IOFI), Flavor and Fragrance Journal, 2011, 26, 297-299 ,

K. Rome et al .: "Intelligent Use of Relative Response Factors in Gas Chromatography Flame Ionization Detection", Chromatography Today, May / June 2012, 52-56 ,

Errors in the gas chromatograph calibration can significantly affect the accuracy of the chromatographic analysis. Thus, due to errors on the part of the user, for example, due to a mistake, wrong calibration mixtures can be used or, for. B. in case of input errors, incorrect information about the calibration mixture are transferred to the evaluation of the gas chromatograph. The calibration mixture itself may have changed due to leaking of the gas cylinder, contamination, aging, so that it no longer complies with the specification. Also, the parameterization of the gas chromatograph may have been changed. Other sources of error are z. B. leaks and faulty flushing of the gas paths of the gas chromatograph.

The invention is therefore based on the object to make the calibration of a gas chromatograph fail-safe.

According to the invention, the object is achieved by the method defined in claim 1 and the gas chromatograph according to claim 7.

Advantageous developments of the method or gas chromatographs according to the invention are specified in the subclaims.

• wobei bei der Kalibrierung eine oder mehrere Proben eines oder mehrerer Kalibriergemische, die die Komponenten in bekannten Konzentrationen enthalten, in dem Gaschromatographen analysiert wird und die relativen Responsefaktoren anhand der erhaltenen Detektorantworten und der bekannten Konzentrationen ermittelt und in der Auswerteeinrichtung abgespeichert werden,

dadurch gekennzeichnet,

• dass bei der Kalibrierung die ermittelten relativen Responsefaktoren in der Auswerteeinrichtung mit für die Detektoreinrichtung typischen universellen relativen Responsefaktoren verglichen werden, und
• dass durch die Auswerteeinrichtung eine Fehlermeldung erzeugt und ausgegeben wird, wenn die bei der Kalibration ermittelten relativen Responsefaktoren von den universellen relativen Responsefaktoren über ein vorgegebenes Maß hinaus abweichen.

The invention thus relates to a method for calibrating a gas chromatograph, which comprises a metering device, a separation device, a detector device and an evaluation device, which are arranged and adapted to meter a sample of a substance mixture to be analyzed, the metered sample for the separation of in the Mixture containing components mixture through the separator to detect at the end of selected separate components and to determine their concentrations in the mixture based on the detector device supplied detector responses and stored in the evaluation device response factors quantitatively, wherein the determination of the concentration of at least a first component of the mixture depending on the detector response to that component, the determined or known concentration of a second component of the mixture and a relative response factor,

• during the calibration, one or more samples of one or more calibration mixtures containing the components in known concentrations are analyzed in the gas chromatograph and the relative response factors are determined based on the detector responses and the known concentrations and stored in the evaluation device,

characterized,

• that during the calibration the determined relative response factors in the evaluation device are compared with universal relative response factors typical for the detector device, and
• an error message is generated and output by the evaluation device if the relative response factors determined during the calibration deviate from the universal relative response factors beyond a predefined amount.

The term "response factor" or "relative response factor" is not to be understood only in the narrow sense of an individual factor, but can also represent a "response function" or "relative response function" over the concentration measuring range, in particular in the case of nonlinear behavior of the detector.

The invention is based on the finding that the detectors used in gas chromatography today have a very high reproducibility due to mass production. This applies in particular to microfabricated (MEMS) detectors, such as. B. Thermal conductivity detectors. Thanks to this high reproducibility, the relative response factors of the detectors are practically invariable and have a universal character. The universal relative response factors can therefore, for. B. at the manufacturer of gas chromatographs and / or detectors, determined for different components and the detectors, for example in the form of a device description, be given or electronically retrievable, for example, on a remote computer accessible on the Internet (cloud) provided. The device description with the universal relative response factors can be stored on a data carrier which can be read by the evaluation device of the gas chromatograph wired and / or wirelessly. For example, the disk as a memory chip, z. B. in the form of an RFID tag, on the detector device or the these forming detectors may be formed.

In the event that deviations exceeding a certain amount are detected in the case of several components, the evaluation device can recognize a deviation pattern and use this information to report a cause of the error. This can be done by comparison with predetermined deviation patterns, which are assigned to different errors.

The invention makes it possible for the user to signal possible errors in the calibration and, if necessary, also to provide information on causes of the error.

To further explain the invention, reference will now be made to the single figure of the drawing which shows an example of a gas chromatograph.

The very simplified gas chromatograph 1 is used for the analysis of a mixture 2, which is removed via a line 3 from a technical process 4. If appropriate, the substance mixture 2 is processed in a processing device 5 for the chromatographic analysis, for example by evaporation, before it is fed to the gas chromatograph 1. In a metering device 6, a sample in the form of the shortest possible and sharply limited Dosierpfropfs is discharged from the mixture 2 and then passed through a separator 8 by means of a carrier gas. The separation device 8 may consist of a single separation column or, as shown here, of a circuit of two or more separation columns 9, 10 in a known manner. As it flows through the separating device 8, the components of the substance mixture 2 contained in the metered sample are separated so that they emerge one after the other from the separating device 8 and are detected by means of a detector device 11. In the example shown, the detector device 11 has two detectors 12, 13, wherein the detector 12 detects a predetermined number of emerging from the separation column 9 and until then sufficiently separated components and the detector 13 detects the remaining components after their separation in the separation column 10 , Possibly. For example, the components detected by the detector 12 may be discharged from the separator 8 before reaching the separation column 10.

The detectors 12, 13 provide as detector signal 14 and 15 each have a chromatogram in which for each component detected a detector response in the form of a peak, z. 16, whose height and area depends on a detection specific property of the component, its amount in the sample, and the detector used. In the exemplary embodiment shown, the detectors 12, 13 are microfabricated (MEMS) thermal conductivity detectors, so that the detection-specific property the component whose thermal conductivity is compared to that of the carrier gas 7. The chromatograms 14, 15 are evaluated in an evaluation device 17 downstream of the detector device 8 in order to determine quantitatively selected components of the substance mixture 2 to be analyzed and finally output them as an analysis result 18. In this case, the concentration of each component is calculated in a computing unit 19 as a function of the respective detector response (peak) 16 to this component and a response factor, which was determined as part of a calibration for the relevant component and stored in a calibration data memory 20.

As already explained above, the response factors generally describe the reaction of the detector to different components, that is, in a single case, the relationship between the concentration of a particular detected component and the resulting detector response. This relationship may be a single value or a concentration-dependent function. Typically, absolute response factors RF indicate the ratio of detector response and concentration. Relative response factors RRF are used to describe the response of the detector to a particular component with respect to the detector's response to another particular component. Typically, a relative response factor RRF indicates the ratio of two response factors RF for different components. If the detector is equal to both components, the relative response factor RRF is equal to one. Relative response factors RRF can be formed from absolute and / or relative response factors RF, RRF.

The response factors RF, RRF are determined as part of a calibration, whereby the gas chromatograph 1 is provided with samples of calibration mixtures 21, 22 which contain components of interest or mixtures of the components with predetermined concentrations. From the detector responses (peaks) 16 generated during the analysis of the calibration samples for the different components and the associated known ones Concentration values, which are input by the user into the evaluation device 17, the evaluation device 17 calculates the response factors RF, RRF and stores them in the calibration data memory 20. For this purpose, the user has available means for input 23 of the known concentration values and visualization 24 of the detector responses processed by the evaluation device 17 (eg keyboard and display, touchscreen, external PC). The determination and storage of the response factors RF, RRF is supported as required by the user and is monitored or carried out automatically. Insofar as this z. B. via an external PC or the like, this can be regarded as part of the evaluation device 17 in the context of the invention. The evaluation device (electronic part) 17 can also be arranged spatially separated from the analysis part of the gas chromatograph 1.

The evaluation device 17 has a further memory 25 in which universal relative response factors uRRF are stored, which have been determined once for the detectors or detector types 12, 13 used and different components. The relative response factors RRF determined during the calibration are compared in a comparator 26 of the evaluation device 17 with the universal relative response factors uRRF, wherein an error message 27 is generated as soon as the relative response factors RRF determined during the calibration exceed the associated universal relative response factors uRRF by a predetermined amount differ. Since, as already explained above, relative response factors for certain components can be converted to other reference components, the comparison also includes those not directly determined by measurement but computationally determined relative response factors RRF and / or universal relative response factors uRRF. The error message 27 and preferably also the amount of deviation are communicated to the user, for. B. displayed on the visualization means 24. In this way, possible errors in the calibration are signaled to the user and, if necessary, also given information on causes of errors. If z. B. at all components a calibration mixture, z. B. 22, an excessive deviation between the determined relative response factors RRF and the associated universal relative response factors uRRF occurs, this may indicate an error in the calibration mixture 22. If deviations occur in the case of several or all calibration mixtures 21, 22, there may be an error in the gas chromatograph 1 or its operation. Singular deviations for individual components indicate a possible input error on the part of the user. On the basis of further deviation patterns, the evaluation device 17 z. B. identify a confusion of the calibration mixtures used as a possible error and notify the user.

The detectors 12, 13 used in the gas chromatograph 1, in particular the microfabricated heat conductivity detectors used here by way of example, have a very high reproducibility due to mass production. Thanks to this high reproducibility, the relative response factors RRF of the detectors 12, 13 are practically invariable and have a universal character. The universal relative response factors uRRF can therefore z. B. manufacturer determined for different components and the detectors, for example in the form of a device description to be given. In the embodiment shown this happens z. B. via a separate disk 28, z. B. USB stick, or a disk, for. Memory chip 29, on the detector 12 'into which the universal relative response factors uRRF are written. This information can be read via a suitable data interface 30 of the evaluation device 17 wired or wireless and transferred to the memory 25. Additionally or alternatively, the universal relative response factors uRRF can be provided on a remote computer 32 (cloud) which can be reached on the Internet 31.

Claims (12)

Method for calibrating a gas chromatograph (1) comprising a metering device (6), a separating device (8), a detector device (11) and an evaluating device (17) which are arranged and designed to produce a sample of a substance mixture to be analyzed (2 ), to pass the metered sample through the separator (8) for separation of components contained in the mixture (2), to detect selected separated components at the end thereof and to determine their concentrations in the mixture (2) by means of the detector means (11 ) and the response factors (RF, RRF) stored in the evaluation device (17), wherein the determination of the concentration of at least one first component of the substance mixture (2) as a function of the detector response (16) to this component, the determined or known concentration of a second component of the substance mixture (2) and a relative response factor rs (RRF), in which calibration one or more samples of one or more calibration mixtures (21, 22) containing the components in known concentrations are analyzed in the gas chromatograph (1) and the relative response factors (RRF) are obtained from the obtained detector responses (16) and the known concentrations are determined and stored in the evaluation device (17), characterized - that in the calibration the determined relative response factors (RRF) in the evaluation device (17) are compared with the detector means (11) typical universal relative response factors (uRRF), and - That the evaluation device (17) generates and outputs an error message (27) if the relative response factors (RRF) determined during the calibration deviate from the universal relative response factors (uRRF) beyond a predefined amount. Method according to claim 1, characterized in that the universal relative response factors (uRRF) of the Manufacturer of the detector device (11) and / or the gas chromatograph (1) are determined and provided. The method of claim 1 or 2, wherein the universal relative response factors (uRRF) are provided in electronic form. Method according to Claim 3, characterized in that the universal relative response factors (uRRF) are provided on a remote computer (32) which can be reached on the Internet (31) and are retrieved by the latter. A method according to claim 1, 2 or 3, characterized in that the universal relative response factors (uRRF) of the detector device (11) are given as a device description. Method according to one of the preceding claims, characterized in that the evaluation device (17) detects a deviation pattern in the event that deviations exceeding a predetermined extent are detected in the case of a plurality of components and reports a cause of the fault on the basis of this. Gas chromatograph (1) comprising a metering device (6), a separating device (8), a detector device (11) and an evaluation device (17) with a calibration data memory (20), which are arranged and designed to be a sample of a substance mixture to be analyzed (2) to meter the metered sample through the separator (8) for separation of components contained in the mixture (2), to detect at the end thereof selected separate components and their concentrations in the mixture (2) from the detector means (11) quantitatively determining the response responses (RF, RRF) stored in the evaluation device (17), wherein the determination of the concentration of at least one first component of the substance mixture (2) as a function of the detector response to this component, certain or known Concentration of a second component of the substance mixture (2) and a relative response factor (RRF) takes place, wherein the evaluation device (17) is further adapted to the relative response factors (RRF) in the calibration of the gas chromatograph (1) with one or more samples of one or more to determine several calibration mixtures (21, 22) containing the components in known concentrations on the basis of the received detector responses (16) and of the known concentrations and to store them in the calibration data memory (20),
characterized,
in that the evaluation device (17) furthermore contains a memory (25) and a comparison device (26), which is designed to contain the relative response factors (RRF) determined in the calibration with the detector device (11) contained in the memory (25) compare relative relative global response factors (uRRF) and generate and output an error message (27) if the relative response factors (RRF) determined during the calibration deviate from the universal relative response factors (uRRF) by more than a predetermined amount. Gas chromatograph (1) according to claim 7, characterized in that the evaluation device (17) has at least one data interface (30, 33) for receiving the universal relative response factors (uRRF). Gas chromatograph (1) according to Claim 8, characterized in that the data interface (33) is designed to receive the universal relative response factors (uRRF) from a remote computer (32) which can be reached in the Internet (31). Gas chromatograph (1) according to claim 8 or 9, characterized in that the data interface (30) is adapted to read the universal relative response factors (uRRF) wired or wirelessly from a data carrier (28, 29). Gas chromatograph (1) according to Claim 10, characterized in that the data carrier consists of a data carrier (29), in particular a memory chip, arranged on the detector device (11). Gas chromatograph (1) according to one of the preceding claims, characterized in that the evaluation device (17) is designed to detect a deviation pattern for the case in which more than the predetermined amount exceeding deviations in several components are detected and based on which a cause of the error Report.

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